The specific scientific goals of the program are: Goal 1. To elucidate the mechanistic basis of environmental carcinogenesis. Although the primary causes of head and neck tumors, lung cancer, and mesothelioma have clearly been identified to be tobacco or asbestos exposure, many important questions remain. These include key issues relating to the molecular mechanisms by which these carcinogens cause cancer, including initiation (carcinogen activation, formation of DNA-adducts and their repair/mis-repair); promotion (changes in cell-cycle check points) and progression, and how multiple carcinogens in complex mixtures e.g., tobacco smoke interact. Goal 2. To elucidate genetic variants and gene-environment interactions that influence susceptibility for lung, airway and aerodigestive cancers. One of the most exciting areas in carcinogenesis research is the ability to now explore small genetic changes (SNPs) in key genes to determine how these changes may alter response to environmental carcinogens. This research has the potential to determine why only some individuals develop cancer after identical exposures. The TEC group is exploring these questions for nicotine addiction and smoking/cancer interactions at multiple levels, including high density SNP arrays for key candidate genes, as well as whole genome scanning. Goal 3. To develop and evaluate interventions to prevent cancer through exposure reduction via tobacco use prevention and cessation. The tobacco research group conducts collaborative translational research that bridges the disciplines of neuroscience, pharmacology, genetics and behavioral science. Through the Center for Interdisciplinary Research on Nicotine Addiction (CIRNA) and other NIH-funded grants, scientists in TEC study youth adoption of smoking, evaluate pharmacotherapies for smoking cessation, within a pharmacogenetics research model, and conduct policy-relevant research on tobacco product harm and marketing. Goal 4. To develop validated biomarkers and imaging approaches that will enable early detection, diagnosis, prognosis, and intervention of environmentally-induced cancers. The goal is to translate our understanding of carcinogenesis and tumor progression into clinically useful approaches for eariy detection, diagnosis, and prognosis of smoking and asbestos-related cancer. The group is exploring genomic changes in peripheral blood mononuclear cells as reporters of disease and novel imaging approaches (fluorine labeled thymidine).